The object of this research is to understand normal glycosphingolipids and glycoprotein metabolism in brain and relate this to the severe neurologic dysfunction seen in children with the inherited inability to catabolize such compounds. Since glycosphingolipids and glycoproteins form an integral part of the glycocalyx of all eukaryotic cells, such studies will also yield information on cell-cell interaction which is crucial to our understanding of tissue rejection and the process of malignancy. Specifically, it is proposed to : 1. Determine the structure and origin of the glycoprotein-like material stored in the liver and brain of patients with four inherited lysosomal hydrolase defieciencies; GM1-gangliosidosis, fucosidosis and mannosidosis. 2. Use this information to devise appropriate remedial therapy, most probably based on enzyme replacement. 3. Study the role of gangliosides and glycoproteins in the formation of dendritic processes by relating morphological changes (caused by addition of neurotransmitters, cydic AMP, etc.) to synthesis of these compounds; this may clarify their role in mental retardation. 4. Use specific inhibitors to block a lysosomal hydrolase so that the effect of a deficient enzyme on some normal neurologic parameters can be assessed.